NM_001009996.3:c.1349T>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001009996.3(DALRD3):c.1349T>C(p.Phe450Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000749 in 1,601,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

DALRD3
NM_001009996.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61

Publications

0 publications found

Variant links:

Genes affected

DALRD3 (HGNC:25536): (DALR anticodon binding domain containing 3) The exact function of this gene is not known. It encodes a protein with a DALR anticodon binding domain similar to that of class Ia aminoacyl tRNA synthetases. This gene is located in a cluster of genes (with a complex sense-anti-sense genome architecture) on chromosome 3, and contains two micro RNA (miRNA) precursors (mir-425 and mir-191) in one of its introns. Preferential expression of this gene (the miRNAs and other genes in the cluster) in testis suggests a role of this gene in spermatogenesis (PMID:19906709). [provided by RefSeq, Feb 2013]

DALRD3 links:

WDR6 (HGNC:12758): (WD repeat domain 6) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. The encoded protein interacts with serine/threonine kinase 11, and is implicated in cell growth arrest. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

WDR6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.961

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009996.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DALRD3	NM_001009996.3	MANE Select	c.1349T>C	p.Phe450Ser	missense	Exon 10 of 12	NP_001009996.1	Q5D0E6-1
DALRD3	NM_018114.6		c.848T>C	p.Phe283Ser	missense	Exon 10 of 12	NP_060584.3
DALRD3	NM_001276405.2		c.1330-7T>C		splice_region intron	N/A	NP_001263334.1	Q5D0E6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DALRD3	ENST00000341949.9	TSL:1 MANE Select	c.1349T>C	p.Phe450Ser	missense	Exon 10 of 12	ENSP00000344989.4	Q5D0E6-1
DALRD3	ENST00000440857.5	TSL:1	c.848T>C	p.Phe283Ser	missense	Exon 11 of 12	ENSP00000403770.1	C9JJG6
DALRD3	ENST00000441576.6	TSL:1	c.1330-7T>C		splice_region intron	N/A	ENSP00000410623.2	Q5D0E6-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000819

AC:

AN:

244346

AF XY:

0.00000759

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000759

AC:

AN:

1449642

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

719260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33300

American (AMR)

AF:

0.00

AC:

AN:

44342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25322

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.00

AC:

AN:

85018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00000906

AC:

AN:

1103718

Other (OTH)

AF:

0.0000167

AC:

AN:

59810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000314

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.96

MetaSVM

Uncertain

0.39

MutationAssessor

Uncertain

2.7

PhyloP100

7.6

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.9

REVEL

Pathogenic

0.91

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.92

MVP

0.90

MPC

0.98

ClinPred

0.99

GERP RS

5.5

BranchPoint Hunter

4.0

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.87

gMVP

0.79

Mutation Taster

=18/82

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over